USP15 Enhances the Proliferation, Migration, and Collagen Deposition of Hypertrophic Scar-Derived Fibroblasts by Deubiquitinating TGF-βR1 In Vitro.
USP15 Enhances the Proliferation, Migration, and Collagen Deposition of Hypertrophic Scar-Derived Fibroblasts by Deubiquitinating TGF-βR1 In Vitro.
复制标题
USP15 通过体外去泛素化 TGF-βR1 增强肥厚性疤痕衍生的成纤维细胞的增殖、迁移和胶原沉积
DOI：
10.1097/prs.0000000000008488
复制
发表时间：
2021-11-01
影响因子：
3.6
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Tu L;Lin Z;Huang Q;Liu D
增生性瘢痕是一种由皮肤损伤引起的纤维增生性疾病。创伤或烧伤后增生性瘢痕的发生率分别为40%至70%或70%。研究表明，转化生长因子β1（TGF β1）/Smad信号通路在增生性瘢痕中起重要作用，而USP 15可通过调节TGFβ1/Smad信号通路的活性而影响疾病的进展。然而，USP 15在增生性瘢痕中的潜在机制仍不清楚。作者推测，USP 15在体外通过去泛素化TGF-β受体I（TβRI）上调并增强增生性瘢痕源性成纤维细胞的增殖、迁移、侵袭和胶原沉积。从体外培养的人增生性瘢痕中分离成纤维细胞。使用慢病毒感染进行肥大性瘢痕来源的成纤维细胞中USP 15的敲低和过表达。采用细胞计数试剂盒-8、划痕法、侵袭法、实时定量聚合酶链反应和Western blot法检测USP 15对增生性瘢痕成纤维细胞增殖、迁移和侵袭的影响，以及对TβRI、Smad 2、Smad 3、α-SMA、COL 1和COL 3表达的影响。免疫共沉淀法和泛素化法检测USP 15与TβRI的相互作用。作者证明，USP 15敲低可显著抑制体外增生性瘢痕成纤维细胞的增殖、迁移和侵袭，并下调TβRI、Smad 2、Smad 3、α-SMA、COL 1和COL 3的表达;此外，USP 15过表达显示相反的趋势（p < 0.05）。免疫共沉淀和泛素化实验表明USP 15与TβRI相互作用并使TβRI去泛素化。USP 15通过去泛素化TβRI促进增生性瘢痕成纤维细胞的增殖、迁移、侵袭和胶原沉积
Hypertrophic scar is a fibroproliferative disorder caused by skin injury. The incidence of hypertrophic scar following trauma or burns is 40 to 70 percent or 70 percent, respectively. It has been shown that transforming growth factor (TGF) β1/Smad signaling plays a crucial role in hypertrophic scar, and that USP15 can regulate the activity of TGFβ1/Smad signaling to affect the progression of the disease. However, the underlying mechanism of USP15 in hypertrophic scar remains unclear. The authors hypothesized that USP15 was up-regulated and enhanced the proliferation, migration, invasion, and collagen deposition of hypertrophic scar–derived fibroblasts by deubiquitinating TGF-β receptor I (TβRI) in vitro. Fibroblasts were isolated from human hypertrophic scars in vitro. The knockdown and overexpression of USP15 in hypertrophic scar–derived fibroblasts were performed using lentivirus infection. The effect of USP15 on hypertrophic scar–derived fibroblast proliferation, migration, and invasion, and the expression of TβRI, Smad2, Smad3, α-SMA, COL1, and COL3, were detected by Cell Counting Kit-8, scratch, invasion, quantitative real-time polymerase chain reaction, and Western blot assays. The interaction between USP15 and TβRI was detected by co-immunoprecipitation and ubiquitination assays. The authors demonstrated that USP15 knockdown significantly inhibited the proliferation, migration, and invasion of hypertrophic scar–derived fibroblasts in vitro and down-regulated the expression of TβRI, Smad2, Smad3, α-SMA, COL1, and COL3; in addition, USP15 overexpression showed the opposite trends (p < 0.05). Co-immunoprecipitation and ubiquitination assays revealed that USP15 interacted with TβRI and deubiquitinated TβRI. USP15 enhances the proliferation, migration, invasion, and collagen deposition of hypertrophic scar–derived fibroblasts by deubiquitinating TβRI in vitro.